Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1.
Using purified recombinant fibronectins we show that WEHI 231 lymphoid cells spread only on fibronectin containing the alternatively spliced V region. Spreading is specifically blocked by peptides from the V25 segment (also called CS-1), which can be selectively spliced out independently of the rest of the V region. Using synthetic peptides we localize the binding site to a 10 amino acid segment that is highly conserved. Integrin alpha 4 beta 1 is a major integrin on the surfaces of these cells and binds specifically to the V25 segment with a primary specificity for the conserved 10 amino acid sequence. Antibodies to integrin alpha 4 inhibit spreading of WEHI 231 cells on V+ fibronectin. Therefore, integrin alpha 4 beta 1 is a fibronectin receptor specific for an alternatively spliced cell adhesion site and may play important roles in selective adhesion of various cell types to specific forms of fibronectin.
Guan
J L
JL
Center for Cancer Research, Department of Biology Massachusetts, Institute of Technology, Cambridge 02139.
Hynes
R O
RO
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes; D002460:Cell Line; D005353:Fibronectins / Q000235:genetics / Q000494:pharmacology*; D016023:Integrins / Q000187:drug effects / Q000502:physiology*; D008223:Lymphoma; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D012326:RNA Splicing; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D010446:Peptide Fragments; D011994:Recombinant Proteins